Leader cells are shown fluorescing green in this photomicrograph. They pull follower cells in their wake as they move to cover and heal a wound. CREDITPak Wong

One of the first things budding biologists get to know is the concept of a single cell. Unlike nerdy biologists who often prefer the company of their lab notebooks, cells are highly social entities that come together to form tissue structures with other identical cells. Just like the humans they constitute, cells have a strong tendency to move around, a process that is known as collective cell migration. Collective cell migration is important in both physiological as well as pathological process such as embryogenesis, Tissue regeneration and cancer metastasis.

In a further extension of the analogy between humans and their constituent cells, collective cell migration often requires the presences of leader cells, who exert mechanical forces on their follower cells to facilitate the process of collective cell migration. Leader cells often tend to stand out by their characteristic features such as larger cell size, ruffling lamellipodium, large focal adhesions and aligned cytoskeletal architecture, features that are geared towards their function as leader cells.

Researchers at the University of Arizona, Tucson, Arizona have analyzed leader cells to identify the features that make them natural leaders during collective cell migration. The study utilized a double stranded locked nucleic acid (dsLNA) assay to study gene expression and identify the molecular signature of leader cells at a single cell level.

The results of the study showed that, leader cells, which often form the tip of migrating cell structures, are characterized not only by high levels of β-Actin mRNA but also Dll4 mRNA, an mRNA that is highly expressed during angiogenesis. The levels of these two mRNAs decrease in the next row of cells and exhibit a Gaussian distribution.

The researchers also showed that these two mRNAs are upregulated in the boundaries of skin puncture wounds in mice. This suggests that leader cells are crucial in closing the wounds and move towards the interior of the wound whilst exerting mechanical force on its followers and facilitating tissue repair. The researchers also clearly established the role of Notch Signaling, an important pathway during embryogenesis and mechanical forces in the establishment of leader cells.

While the existence of leader cells has been known, this is one of the first studies that explains the factors involved in the formation of leader cells. The researchers also showed that the migration rate of cells is directly correlated to the leader cell density. It is also postulated that this mechanism of collective cell migration is likely to be utilized by the body when there are large punctures.

Shruti Srinivasan is a 4th year Ph.D. student at the National University of Singapore. In addition to Epigenetics, her primary research interest, she cares deeply about education, equal representation of women and healthcare. Shruti wishes to invest her time and effort advocating for these causes in the future. She is also interested in opportunities in life science consulting